Posttraumatic Stress Disorder and Obstructive Sleep Apnea in Twins

Key Points Question What is the association of posttraumatic stress disorder (PTSD) with obstructive sleep apnea (OSA) after accounting for acknowledged medical risk factors for OSA? Findings In a cross-sectional study of 132 older male veteran twins discordant for PTSD undergoing in-laboratory polysomnography, current PTSD diagnosis and symptoms were associated independently with OSA, even after controlling for demographics, behavioral factors, cardiovascular risk factors, and familial factors. Meaning These findings suggest that PTSD may be an independent, novel, and heretofore unrecognized risk factor for OSA in older men.


Statistical Methods
We used twin models (figure 1) to help control for familial factors in the investigation of the relationship between PTSD and obstructive sleep apnea.Examples of familial factors include socioeconomic status, family history, parental factors, prenatal and early life experiences, culture, and geography.In addition, because the twins were enrolled together and traveled at the same time, we were able to control for variations due to visit date, staff, season, travel, and other environmental exposures.In monozygotic twin pairs, we can also fully control for genetic factors, while in dizygotic twin pairs, we can only partially control for genetic factors (half, on average).Because of our limited ability to examine differences by zygosity due to the small sample size of discordant twin pairs, we included partial to full genetic effects within the umbrella of familial factors.Not only may unaccounted familial factors partially confound the results, but they may also increase random error that can reduce the precision of the results (reduced internal consistency).
Our analyses focused on complete pairs of twins in which the PCL score differed by at least one point, which we defined as PCL discordant pairs.Therefore, we excluded twin pairs where the scores were exactly the same.In most PCL-concordant cases, both twins had a PCL score of 0.
For each variable used in the analysis, we calculated the pair average, and then the within-pair difference by calculating the difference between the individual twin value and the between-pair mean as shown in figure 2   Step 1: Create pair average.
Step 2: Create within-pair differences for each participant.

Environmental confounders
Similarly, we measured within-pair differences for the co-variates and outcomes.This allowed us to use the following linear regression model using generalized estimating equations, as also discussed by Carlin 2005 (reference above): Difference in AHI = Intercept + Beta( 1)*(Within-pair PCL-5 difference) + Beta( 2)*(Within pair covariate difference)… Our interpretation of this model was that each unit increment of the difference in PCL-5 score (which was re-scaled to 15-point difference to provide a meaningful clinical difference) was associated with a Beta(1) difference in AHI between brothers while controlling by design for demographic, familial and certain environmental confounders, as well as adjusting for covariates in the model. © below.These methods have been described in more detail here: Carlin et al., Int J Epidemiol.2005 Oct; 34(5):1089-99.Doi: 10.1093/ije/dyi153.

Figure 2 -
Figure 2 -How we created within-pair difference variables.

Figure 1 :
Figure 1: Model of twin models that control for familial confounding by design.Control for environmental factors requires regression models that control for their effects.

Table 1a :
Association of PCL-5 Score with AHI (fully adjusted, non-standardized) 2024 Shah AJ et al.JAMA Network Open.© 2024 Shah AJ et al.JAMA Network Open.

Table 2a :
Association of PTSD Status with AHI, adjusting for psychiatric factors

Table 2b :
Association of PTSD Status with AHI, adjusting for cardiac factors Association of PCL-5 Score With AHI, Examining for Interaction With Zygosity © 2024 Shah AJ et al.JAMA Network Open.© 2024 Shah AJ et al.JAMA Network Open.eTable 4.

Table 5a .
Association of PTSD with AHI, examining for zygosity interaction and adjusting for cardiac factors

Table 5b .
Association of PTSD with AHI, examining for zygosity interaction and adjusting for psychiatric factors Directed Acyclic Graph for Multivariable Models* *All models adjust for age and familial factors.In addition, model 2 adjusts for possible CVD risk factors and CVD history, while model 3 adjusts for potential confounders that include demographic and psychiatric factors.Abbreviations: PTSD=posttraumatic stress disorder; CVD=cardiovascular disease; OSA=obstructive sleep apnea; BDI=Beck Depression Inventory; ETOH=alcohol; BMI=body mass index; HTN=hypertension; DM=diabetes mellitus; HL=hyperlipidemia; PA=Baecke physical activity index